Reprogramming of Metabolic and Adipokine-related Gene Expression in 3D Mammary Epithelial Organoids by Dietary Bioactive Compounds
摘要
Dietary bioactive compounds can modulate mammary gland gene expression, potentially influencing milk composition and infant metabolic programming. This study investigated whether selected dietary bioactive compounds modulate leptin and adiponectin expression in rat mammary epithelial organoids (MEO), a 3D in vitro model of the mammary gland. 18 nutrients were initially screened for effects on leptin gene expression, followed by confirmatory and dose-dependent analyses focusing on oleic acid (OA), leucine (Leu), betaine (Bet), and their triple combination. mRNA levels of leptin, adiponectin, and β-casein (Csn2), as well as selected genes related to one-carbon and lipid metabolism and specific microRNAs, were analyzed. OA, alone or in combination, consistently increased leptin, adiponectin, and Csn2 mRNA expression in MEO compared with controls. These effects were accompanied by downregulation of lipogenic markers, including Srebp1, and increased Cpt1b expression under the triple-combination treatment, without significant changes in miRNA levels. In contrast, Bet and Leu showed more variable, context-dependent effects on leptin, adiponectin, and Csn2 expression, while altering miRNA profiles that differed from those observed under OA-containing treatments. Overall, the results indicate that dietary bioactive compounds modulate gene expression of rat MEO.